Motivated by important applications in materials science and biology, we consider a non-stationary coagulation equation with in-flux and out-flux of particles (cargo). An exact analytical solution to this integrodifferential equation is found in a parametric form. This solution behaves as a decaying exponent with respect to the particle volume (fluorescence intensity in the case of coagulation of endosomes). We demonstrate that our exact solution substantially depends on coagulation kernels (fusion and fission rates) as well as the in-flux and out-flux processes of cargo.
Objective: To investigate the compatibility of oxytocin and tranexamic acid injection products when mixed for the purpose of co-administration by intravenous infusion. Population or Sample: Oxytocin and tranexamic acid were collected from hospitals taking part in a multicentre postpartum haemorrhage treatment (E-MOTIVE) trial in Kenya, Nigeria, Tanzania, and South Africa. Methods: The compatibility of two sentinel products of oxytocin injection and tranexamic acid injection in 200mL infusion bags of both 0.9%w/v saline and Ringer’s Lactate was assessed. We analysed all tranexamic acid -oxytocin combinations, and each evaluation was conducted for up to 6hrs. Subsequently, the compatibility of multiple tranexamic acid products with reference oxytocins products when mixed in 0.9%w/v saline over a period of 1 hour was investigated. Results: We found a significant interaction between certain oxytocin and tranexamic acid products after mixing them in vitro and observing for 1 hour. The interaction substantially impacted oxytocin content leading to reduction in concentration (14.8% - 29.0%) immediately on mixing (t=0 minutes). In some combinations, the concentration continued to decline throughout the stability assessment period. Oxytocin loss was observed in 7 out of 22 (32%) combinations tested. Conclusions: In a clinical setting, mixing oxytocin and tranexamic acid may result in an underdosing of oxytocin, compromising care in an emergency life-threatening situation. The mixing of oxytocin and tranexamic acid injection products for co-administration with IV infusion fluids should be avoided until the exact nature of the interaction and its implications are understood.
The effect of antenatal depressive and anxious symptoms on the rate of physiological birthsA comment on the recently published article by Hulsbosch et al:Association between high levels of comorbid anxiety and depressive symptoms and decreased likelihood of birth without intervention: A longitudinal prospective cohort study
Hemorrhagic cystitis is a common complication following the use of cyclophosphamide. Associated dysuria can be painful and there are few good options to relive pain. Phenazopyridine has historically been utilized for dysuria and is available over the counter. However, it is associated with hematologic side effects with prolonged use.
An accurate medication history prevents medication errors during transitions of care, whereas an inaccurate medication history may lead to unnecessary tests or prolonged hospitalization. We describe the case of a patient with chronic hypothyroidism who presented to the hospital with severe hypothyroidism and reported strict adherence to her home levothyroxine.
Acute Lymphoblastic Leukemia of the Central Nervous System Presenting with Rapid Weight GainConnor P. Hall1 and Alan D. Friedman11Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USACorrespondence: Alan D. Friedman, MDJohns Hopkins UniversityCRB I, Rm. 253 1650 Orleans St. Baltimore, Maryland 21231 Phone: 410-955-2095; Fax: 410-955-8897 Email: [email protected] Count: 863Number of Figures: 1Running Title: Rapid Weight Gain in ALLKey Words: acute lymphoblastic leukemia/ relapse/ weight gain/ central nervous systemAbbreviations:
Wolves (Canis lupus) can exert top-down pressure and shape ecological communities through selective predation of ungulates and beavers (Castor Canadensis). Considering their ability to shape communities through predation, understanding wolf foraging decisions is critical to predicting their ecosystem level effects. Specifically, if wolves are optimal foragers, consumers that optimize tradeoffs between cost and benefits of prey acquisition, changes in these factors may lead to prey switching or negative-density dependent selection with potential consequences for community stability. For wolves, factors affecting cost and benefits include prey vulnerability, risk, reward, and availability which can vary temporally. We described wolf diet in by frequency of occurrence and percent biomass and characterized diet in relation to optimal foraging using prey remains found in wolf scats on Isle Royale National Park, Michigan, USA during May–October 2019–2020. We used logistic regression to estimate prey consumption over time. We predicted prey with temporal variation in cost (vulnerability and/or availability) such as adult and calf moose (Alces alces) and beaver to vary in wolves’ diet. We analyzed 206 scats and identified 62% of remains as beaver, 26% as and moose, and 12% as other (birds, smaller mammals, and wolves). Adult moose were more likely to occur in wolf scat in May, when moose are in poor condition following winter. Similarly, the occurrence of moose calves peaked June–mid July following parturition but before their vulnerability declined as they matured. In contrast, beaver occurrence in wolf scat did not change over time, possibly reflecting the importance of low handling cost prey items for recently introduced lone or paired wolves. Our results demonstrate that wolf diet is plastic and responsive to temporal changes in prey acquisition cost as predicted by optimal foraging theory. Temporal fluctuation in diet may influence wolves’ ecological role if prey respond to increased predation risk by altering their foraging or breeding behavior.
The objective of the study was to simulate New Zealand’s foot-and-mouth disease (FMD) operational plan to determine personnel requirements for a FMD response and understand how the numbers of frontline staff available could affect the size and duration of FMD outbreaks, when using stamping-out (SO) measures with or without vaccination. The model utilized a national dataset of all known livestock farms. Each simulation randomly seeded infection into a single farm. Transmission mechanisms included direct and indirect contacts, local and airborne spread. Prior to each simulation, the numbers of personnel for front-line tasks were set randomly. In a random subset of simulations, vaccination was allowed to be deployed as an adjunct to SO. Front-line tasks included contact tracing, surveillance of at-risk farms, depopulation and vaccination using teams comprising personnel of the different types required by New Zealand’s operational plans. The effect of personnel numbers on the size and duration of epidemics were explored using machine learning methods. In the second stage of the study, using a subset of iterations where numbers of personnel were unconstrained, the number of personnel used each day were quantified. When personnel resources were unconstrained, the 95 th percentile and maximum number of infected places (IPs) were 78 and 462 respectively, and the 95 th percentile and maximum duration were 69 and 217 days respectively. However, severe constraints on personnel resources allowed some outbreaks to exceed the size of the UK 2001 FMD epidemic which had 2026 IPs. The number of veterinarians available had a major influence on the size and duration of outbreaks, while the availability of other personnel types did not. A shortage of veterinarians was associated with an increase in time to detect and depopulate IPs, allowing for continued transmission. Emergency vaccination placed a short-term demand for additional staff at the start of the vaccination programme, but the overall number of person days used were similar to SO-only strategies. This study determined the optimal numbers of front-line personnel required to implement the current operational plans to support an FMD response in New Zealand. A shortage of veterinarians was identified as the most influential factor to impact disease control outcomes. Emergency vaccination led to earlier control of an FMD outbreak, but also resulted in a short-term spike in demand for personnel. A successful response needs to have access to sufficient personnel, particularly veterinarians, trained in response roles and available at short notice.
Objectives: New temperature management concepts of moderate and mild hypothermic circulatory arrest during aortic arch surgery have gained weight over profound cooling. Comparisons of all temperature levels have rarely been performed. We performed direct and indirect comparisons of deep hypothermic circulatory arrest (DHCA) (≤20°C), moderate hypothermic circulatory arrest (MHCA) (20.1°C to 25°C), and mild hypothermic circulatory arrest (mild HCA) (≥25.1°C) in a network meta-analysis. Methods: The literature was systematically searched for all papers published through February 2022 reporting on clinical outcomes after aortic arch surgery utilizing DHCA, MHCA and mild HCA. The primary outcome was operative morality. The secondary outcomes were postoperative stroke and acute kidney failure (AKI). Results: A total of 34 studies were included, with a total of 12 370 patients. DHCA was associated with significantly higher postoperative incidence of stroke when compared with MHCA (odds ratio (OR), 1.46, 95% (confidence interval) CI, 1.19-1.78) and mild HCA: (OR, 1.50, 95% CI, 1.14-1.98). Furthermore, DHCA and MHCA were associated with higher operative mortality when compared with mild HCA (OR 1.71, 95% CI, 1.23-2.39 and OR 1.50, 95% CI, 1.12-2.00, respectively). Separate analysis of randomized and propensity score matched studies showed sustained increased risk of stroke with DHCA in contrast to MHCA and mild HCA (OR, 1.61, 95% CI, 1.18-2.20, P-value = 0.0029 and OR, 1.74, 95% CI, 1.09-2.77, P-value = 0.019). Conclusions: In the included studies, the moderate to mild hypothermia strategies were associated with decreased operative mortality and the risk of postoperative stroke. Large-scale prospective studies are warranted to further explore appropriate temperature management for the treatment of aortic arch pathologies.
Over the last two decades, there has been a huge increase in our understanding of microbial diversity, structure and composition enabled by high throughput sequencing (HTS) technologies. Yet, it is unclear how the number of sequences translates to the number of cells or species within the community. Additional observational data may be required to ensure relative abundance patterns from sequence reads are biologically meaningful or presence absence data may be used instead of abundance. The goal is to obtain robust community abundance data, simultaneously, from environmental samples. In this issue of Molecular Ecology Resources, Karlusich et al., (2022) describe a new method for quantifying phytoplankton cell abundance. Using Tara Oceans datasets, the authors propose the photosynthetic gene psbO for reporting accurate relative abundance of the entire phytoplankton community from metagenomic data. The authors demonstrate improved correlations with traditional optical methods including microscopy and flow cytometry, improving upon current molecular identification typically using rRNA markers genes. Furthermore, to facilitate application of their approach, the authors curated a psbO gene database for accessible taxonomic queries. This is an important step towards improving species abundance estimates from molecular data and eventually reporting of absolute species abundance, enhancing our understanding of community dynamics.
Pena-Shokeir Syndrome is considered to be a fatal congenital condition that is rarely diagnosed in neonates. We present the first ever reported case of Pena-Shokeir Syndrome from Syria. Both clinical assessment and early prenatal diagnosis are necessary to give more realistic options for the mother and the baby.
Background and Purpose: ISX9 is a neurogenesis-promoting small molecule compound which can upregulate the expression of NeuroD1 and induce differentiation of neuronal, cardiac and islet endocrine progenitors. So far, the molecular mechanisms underlying the action of ISX9 still remain elusive. Experimental Approach: To identify a novel agonist of the Wnt/β‐catenin, a cell-based SuperTOPFlash reporter system was used to screen known-compound libraries. An activation effect of ISX9 on the Wnt/β‐catenin pathway was analysed with the SuperTOPFlash or SuperFOPFlash reporter system. Effects of ISX9 on Axin1/LRP6 interaction were examined using a mammalian two-hybrid system, co‐immunoprecipitation, microscale thermophoresis (MST), emission spectra and mass spectroscopy assays. The expression of Wnt target and stemmness marker genes were evaluated with real‐time PCR and immunoblotting. In vivo hair regeneration abilities of ISX9 were analysed by immunohistochemical staining, real‐time PCR and immunoblotting in hair regrowth model using C57BL/6J mice. Key Results: In this study, ISX9 was identified as a novel agonist of the Wnt/β‐catenin pathway. ISX9 targeted Axin1 by covalently binding to its N-terminal region and potentiated the LRP6-Axin1 interaction, thereby resulting in the stabilization of β‐catenin and upregulation of Wnt target genes and stemmness marker genes. Moreover, the topical application of ISX9 markedly promoted hair regrowth in C57BL/6J mice and induced hair follicle transition from telogen to anagen via enhancing Wnt/β‐catenin pathway. Conclusions and Implications: Taken together, our study unraveled that ISX9 could activate Wnt/β‐catenin signaling by potentiating the association between LRP6 and Axin1, and may be a promising therapeutic agent for alopecia treatment
The analysis of genomic data can be an intimidating process, particularly for researchers who are not experienced programmers. Commonly used analyses are spread out across programs, each of which require their own input formats, and data must often be wrangled and re-wrangled into new formats to split the data according to categorical metadata variables, such as population or family. Here, we introduce snpR, and R package that allows for user-friendly processing of SNP genomic data by automating data sub-setting and processing across categorical metadata, integrating approaches contained in many different packages under a single ecosystem, and allowing for iterative, efficient analysis focused on a single R object across an entire analysis pipeline.
1. Given the sharp increase in agricultural and infrastructure development and the paucity of widespread data available for making conservation management decisions, a more rapid and accurate tool for identifying fish fauna in the world’s largest freshwater ecosystem, the Amazon, is needed. 2. Current strategies for identification of freshwater fishes require high levels of training and taxonomic expertise for morphological identification or genetic testing for species recognition at a molecular level. 3. To overcome these challenges, we built an image masking model (U-Net) and a convolutional neural net (CNN) to classify Amazonian fish in photographs. Fish used as training data were collected and photographed in tributaries in seasonally flooded forests of the upper Morona River valley in Loreto, Peru in 2018 and 2019. 4. Species identifications in the training images (n = 3,068) were verified by expert ichthyologists. These images were supplemented with photographs taken of additional Amazonian fish specimens housed in the ichthyological collection of the Smithsonian’s National Museum of Natural History. 5. We generated a CNN model that identified 33 genera of fishes with a mean accuracy of 97.9%. Wider availability of accurate freshwater fish image recognition tools, such as the one described here, will enable fishermen, local communities and community scientists to more effectively participate in collecting and sharing data from their territories to inform policy and management decisions that impact them directly.
Background: Acute type A aortic dissection (ATAAD) is a life-threatening medical condition requiring urgent surgical attention. It is estimated that 50% of ATAAD die within 24 hours of onset, with the mortality rate is increasing by 1-2% every additional hour without prompt intervention. A variety of ATAAD surgical repair techniques exist which has sparked controversy within the literature, with the main two strategies being proximal aortic replacement (PAR) and total arch replacement (TAR). Nevertheless, the question of which of these two strategies if the more optimal is still debatable. Aims: This commentary aims to discuss the recent study by Sa and colleagues which presents a pooled analysis of Kaplan-Meier-derived individual patient data from studies with follow-up comparing aggressive (TAR) and conservative (PAR) approaches to manage ATAAD patients. Methods: A comprehensive literature search was performed using multiple electronic databases including PubMed, Ovid, Google Scholar, EMBASE and Scopus in order to collate the relevant research evidence. Results: The more aggressive TAR approach for treating ATAAD seems to yield more favourable results including more optimal long-term survival as well as a lower need for reoperation. The frozen elephant trunk (FET) technique can be considered the mainstay TAR technique. Conclusion: It is valid to conclude that TAR with FET is the superior strategy for managing ATAAD patients.
Tracheo-innominate fistula (TIF) is a reported complication of tracheostomy that typically presents with a herald bleed. The phenomenon of an aorto-tracheal fistula has similar pathology and presentation to TIF, but no standard surgical repair. In the manuscript by Musgrove et al. in the Journal of Cardiac Surgery the authors propose a surgical treatment, that is reproduceable for the correct anatomic configuration - an ascending and aortic arch replacement, pericardial patch of the tracheal defect, and omental flap coverage to prevent infection. While this intervention seems a large undertaking for a small defect, it is a safe and durable repair.
Frozen elephant trunk (FET) has in recent times become a mainstay for total arch replacement (TAR) in aortovascular surgery and is indicated in order to treat a spectrum of complex aortic pathologies. However, despite associated excellent post-operative results it is incredibly important to recognise potential adverse complications such as negative aortic remodelling, endoleak and distal stent-graft induced new entry so that outcomes can be further improved. Below we provide commentary on a recent article in the Journal of Cardiac Surgery discussing the topic. Despite the fascinating outcomes of this systematic review and meta-analysis the heterogeneity of the literature regarding these adverse outcomes remains an issue which can only be solved with large multi-centre trials directly comparing graft types as well as indications for surgery.